1. Field of the Invention
The present invention generally relates to methods and devices for sorting particles in a fluid using a fluid displacer in a closed-loop.
2. Description of the Related Art
In the fields of biotechnology, and especially cytology and drug screening, there is a need for high throughput sorting of particles. Many prior art methods and devices for particle sorting are based on the detect-decide-deflect principle in which moving particles suspended in a liquid flowing through a channel network having at least a branch point downstream are first analyzed for a given characteristic and then deflected according to the characteristic in the direction of a predetermined branch or area of the channel network.
Numerous sorting strategies for micro fluidic-based particle sorting are known in the art. Some prior art sorting techniques include electrokinetic flow switching (see e.g. Fu et al. (1999) Nature Biotech. 17:1109-1111 and Dittrich et al. (2003) Anal. Chem. 75:5767-5774); hydrodynamic flow switching using on-chip (see e.g. Fu et al. (2002) Anal. Chem. 74:2451.2457) and off-chip valves (see e.g. Kruger et al. (2002) Micromech. & Microengineer. 12:486-494 and Wolff et al. (2003) Lab on a Chip 3:22-27); MEMS-based micro-T switches (see e.g. Ho et al. (2005) Lab on a Chip 5:1248-1258); and a thermoreversible gelation polymer (see e.g. Shirasaki et al. (2006) Anal. Chem. 78:695-701). Dielectrophoretic approaches for cell sorting include segregation of tagged cells (see e.g. Hu et al. (2005) PNAS USA 102:15757-15761); untagged cells (see e.g. Lapizco-Encinas et al. (2004) Anal. Chem. 76:1571-1579, and Kim et al. (2007) PNAS USA 104:20708-20712) and droplets (and Ahn et al. (2006) Applied Physics Letts 88:24104-24101. Optical sorting has been achieved by binning particles into one (see e.g. Tu et al. Optical Trapping and Optical Micromanipulation; Dholakia, K., Spalding, G. C., Eds., 2004; Vol. 5514, pp 774-785, Wang et al. (2005) Nature Biotech. 23:83-87, and Perroud et al. (2008) Anal. Chem. 80:6365-6372) or more channels (see e.g. Applegate et al. (2006) Lab on a Chip 6:422-426) and manipulating individual cells within an array of microwells (see e.g. Luo et al. (2007) Biomedical Microdevices 9:573-578 and Kovac et al. (2007) Anal. Chem. 79:9321-9330); and Cho et al. (2008) Proc. of SPIE 7135:71350 M1-10).
Some prior art methods employ a piezoelectric element to shift the fluid surrounding the particle of interest towards a desired area, thereby sorting or separating the particle of interest from other particles in the fluid flow that has not been shifted. See, for example, U.S. Pat. Nos. 7,157,274; 7,312,085; 7,389,879; and 7,392,908.
Unfortunately, these prior art piezoelectric-based sorters suffer from creating a transient pressure gradient during the deflection affecting the steady-state flow stream upstream and downstream of the deflection region. Since the detection region is upstream of the deflection region, the velocity and trajectory of subsequent particles is affected by the deflection of the particle of interest. This change in velocity or trajectory creates a jitter effect in the detection region affecting the accuracy of the detection.
Therefore, a need exists for methods and devices which sort individual particles with high efficiency and throughput in a cost-effective way without disturbing the flow pattern upstream, downstream, or both of the deflection region.